NM_001048174.2(MUTYH):c.1322T>C (p.Val441Ala) AND Familial adenomatous polyposis 2

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 26, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003613708.1

Allele description

NM_001048174.2(MUTYH):c.1322T>C (p.Val441Ala)

Gene:

MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_001048174.2(MUTYH):c.1322T>C (p.Val441Ala)

HGVS:

NC_000001.11:g.45331252A>G
NG_008189.1:g.14219T>C
NM_001048171.2:c.1322T>C
NM_001048172.2:c.1325T>C
NM_001048173.2:c.1322T>C
NM_001048174.2:c.1322T>CMANE SELECT
NM_001128425.2:c.1406T>C
NM_001293190.2:c.1367T>C
NM_001293191.2:c.1355T>C
NM_001293192.2:c.1046T>C
NM_001293195.2:c.1322T>C
NM_001293196.2:c.1046T>C
NM_001350650.2:c.977T>C
NM_001350651.2:c.977T>C
NM_001407069.1:c.1355T>C
NM_001407070.1:c.1322T>C
NM_001407071.1:c.1325T>C
NM_001407072.1:c.1322T>C
NM_001407073.1:c.1322T>C
NM_001407075.1:c.1238T>C
NM_001407077.1:c.1355T>C
NM_001407078.1:c.1325T>C
NM_001407079.1:c.1283T>C
NM_001407080.1:c.1280T>C
NM_001407081.1:c.1322T>C
NM_001407082.1:c.977T>C
NM_001407083.1:c.1364T>C
NM_001407085.1:c.1364T>C
NM_001407086.1:c.1325T>C
NM_001407087.1:c.1343T>C
NM_001407088.1:c.1322T>C
NM_001407089.1:c.1322T>C
NM_001407091.1:c.1046T>C
NM_012222.3:c.1397T>C
NP_001041636.2:p.Val441Ala
NP_001041637.1:p.Val442Ala
NP_001041638.1:p.Val441Ala
NP_001041639.1:p.Val441Ala
NP_001121897.1:p.Val469Ala
NP_001121897.1:p.Val469Ala
NP_001280119.1:p.Val456Ala
NP_001280120.1:p.Val452Ala
NP_001280121.1:p.Val349Ala
NP_001280124.1:p.Val441Ala
NP_001280125.1:p.Val349Ala
NP_001337579.1:p.Val326Ala
NP_001337580.1:p.Val326Ala
NP_001393998.1:p.Val452Ala
NP_001393999.1:p.Val441Ala
NP_001394000.1:p.Val442Ala
NP_001394001.1:p.Val441Ala
NP_001394002.1:p.Val441Ala
NP_001394004.1:p.Val413Ala
NP_001394006.1:p.Val452Ala
NP_001394007.1:p.Val442Ala
NP_001394008.1:p.Val428Ala
NP_001394009.1:p.Val427Ala
NP_001394010.1:p.Val441Ala
NP_001394011.1:p.Val326Ala
NP_001394012.1:p.Val455Ala
NP_001394014.1:p.Val455Ala
NP_001394015.1:p.Val442Ala
NP_001394016.1:p.Val448Ala
NP_001394017.1:p.Val441Ala
NP_001394018.1:p.Val441Ala
NP_001394020.1:p.Val349Ala
NP_036354.1:p.Val466Ala
LRG_220t1:c.1406T>C
LRG_220:g.14219T>C
LRG_220p1:p.Val469Ala
NC_000001.10:g.45796924A>G
NM_001128425.1:c.1406T>C
NR_146882.2:n.1550T>C
NR_146883.2:n.1399T>C
NR_176269.1:n.1546T>C
NR_176270.1:n.1486T>C
NR_176271.1:n.1409T>C
NR_176272.1:n.1473T>C
NR_176273.1:n.1431T>C
NR_176274.1:n.1486T>C

Protein change:

V326A

Molecular consequence:

NM_001048171.2:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1325T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1406T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1367T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1355T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.1046T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.1046T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.977T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.977T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407069.1:c.1355T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407070.1:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407071.1:c.1325T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407072.1:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407073.1:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407075.1:c.1238T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407077.1:c.1355T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407078.1:c.1325T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407079.1:c.1283T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407080.1:c.1280T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407081.1:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407082.1:c.977T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407083.1:c.1364T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407085.1:c.1364T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407086.1:c.1325T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407087.1:c.1343T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407088.1:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407089.1:c.1322T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407091.1:c.1046T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1397T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1550T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1399T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176269.1:n.1546T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176271.1:n.1409T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176272.1:n.1473T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176273.1:n.1431T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176274.1:n.1486T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Familial adenomatous polyposis 2
Synonyms:: COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; MYH-associated polyposis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012041; MedGen: C3272841; Orphanet: 220460; OMIM: 608456

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Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004489968	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 26, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004489968

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 26, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004489968.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 469 of the MUTYH protein (p.Val469Ala).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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